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Molecular pharmacological studies on the expression of synaptic plasticity

Research Project

Project/Area Number 04670124
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field General pharmacology
Research InstitutionKumamoto University

Principal Investigator

FUKUNAGA Kohji  Kumamoto University, Pharmacology, Associate Professor, 医学部, 助教授 (90136721)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Hideyuki  Kumamoto University, Pharmacology, Assistant Professor, 医学部, 講師 (60191433)
MIYAMOTO Eishichi  Kumamoto University, Pharmacology, Professor, 医学部, 教授 (50109659)
太田 安隆  熊本大学, 医学部, 助手 (90192517)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1992: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsHippocampus / Memory / Learning / Synaptic long-term potentiation / Glutamate receptor / NMDA receptor / Ca^<2+> mobilization / CaM kinase II / 蛋白質燐酸化反応 / 培養細胞
Research Abstract

Long-term potentiation (LTP) is a form of synaptic plasticity widely investigated as a molecular basis of the memory formation. Studies on several protein kinase inhibitors have indicated a role of Ca^<2+>/calmodulin-dependent protein kinase II(CaM kinase II) in LTP of hippocampus. We hypothesized that elevation of intracellular Ca^<2+> through NMDA receptor activation would trigger autophosphorylation of CaM kinase II to form its Ca^<2+>-independent species, which would remain active even when the intracellular Ca^<2+> was resequestered to its basal level. In cultured hippocampal neurons, activation of NMDA receptor increased the Ca^<2+>-independent activity of CaM kinase II and in turn stimulated the phosphorylation of target proteins such as microtuble-associated protein 2 and synapsin I.Furthermore, high frequency stimulation applied to Cal afferents in the hippocampal slices resulted in the induction of LTP with concomitant long-lasting increases in the Ca^<2+>-independent and total CaM kinase II activities as well as an increases in the ratio of Ca^<2+>-independent to total activity. The effect was obtained using two different CaM kinase II substrates, syntide 2 and synapsin I, and it was observed in hippocampal slices and hippocampal organotypic cultures. The treatment of slices with NMDA receptor antagonist, D-2-amino-5-phosphonopentanoate prevent LTP induction and abolished the increase in the Ca^<2+>-independent activity as well as the increase in the total activity. These finding suggest that CaM kinase II can act as an important molecule for the formation of the hippocampal LTP.

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] K.Fukunaga: "Activation of Ca^<2+>/calmodulin-dependent protein kinase II and protein kinase C by glutamate in cultured rat hippocampal neurons" J.Biol.Chem.267. 22527-22533 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] K.Fukunaga: "Dephosphorylation of autophosphorylated Ca^<2+>/calmodulin-dependent protein kinase II by protein phosphatase 2C" J.Biol.Chem.268. 133-137 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] K.Fukunaga: "Long-term potentiation is associated with an increased activity of Ca^<2+>/calmodulin-dependent protein kinase II" J.Biol.Chem.268. 7863-7867 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 福永浩司: "細胞情報伝達機構におけるCa^<2+>/カルモデュリン依存性プロテインキナーゼの役割" 日薬理誌. 101. 355-369 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] F.Arakane: "Glycolipids isolated from Aplysia kurodai can activate cyclic adenosine 3′,5′-monophosphate-dependent protein kinase from rat brain" J.Neurochem. 62. 86-93 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Yano: "Activation of Ca^<2+>/calmodulin-dependent protein kinase II and phosphorylation of intermediate filament proteins by stimulation of glutamate receptors in cultured rat cortical astrocytes" J.Biol.Chem.269. 5428-5439 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] K.Fukunaga: "In:Fidia Research,Foundation Symposium Series,Vol.9,Excitatory amino acids(Eds.R.P.Simon),Excitatory amino acids and protein kinases" Thieme Medical Publishers,Inc.,New York, 7 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] H.Yamamoto, K.Fukunaga, K.Lee & T.R.Soderling: "Ischemia-induced loss of brain calcium/calmodulin-dependent protein kinase II" J.Neurochem.58. 1110-1117 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] M.Morioka, K.Fukunaga, S.Yasugawa, S.Nagahiro, Y.Ushio & E.Miyamoto: "Regional and temporal alterations in Ca^<2+>/calmodulin-dependent protein kinase II and calcineurin in the hippocampus of rat brain after transient forebrain ischemia" J.Neurochem.58. 1798-1809 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] T.Yamakawa, K.Fukunaga, H.Hatanaka & E.Miyamoto: "Occurrence of Ca^<2+>/calmodulin-dependent protein kinase II in various cultured cells" Biomedical Res.13. 173-179 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] B.A.Perrino, Y.-L.Fong, D.A.Brickey, Y.Saitoh, Y.Ushio, K.Fukunaga, E.Miyamoto & T.R.Sodering: "Characterization of the phosphatase activity of a baculovirus-expressed calcineurin A isoform" J.Biol.Chem.267. 15965-15969 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] T.Yamakawa, K.Fukunaga, H.Higashida & E.Miyamoto: "Activation of Ca^<2+>/calmodulin-dependent protein kinase II by stimulation with bradykinin in neuroblastoma X glioma hybrid NG108-15 cells" Brain Res.597. 220-226 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] K.Kugiyama, M.Ohgushi, S.Sugiyama, T.Murohara, K.Fukunaga, E.Miyamoto & H.Yasue: "Lysophosphatidylcholine inhibits surface receptor-mediated intracellular signals in endotherial cells by a pathway involving protein kinase C activation" Circulation Res.71. 1422-1428 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] K.Fukunaga, T.R.Soderling & E.Miyamoto: "Activation of Ca^<2+>/calmodulin-dependent protein kinase II and protein kinase C by glutamate in cultured rat hippocampal neurons" J.Biol.Chem.267. 22527-22533 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] K.Fukunaga, T.Kobayashi, S.Tamura & E.Miyamoto: "Dephosphorylation of autophosphorylated Ca^<2+>/calmodulin-dependent protein kinase II by protein phosphatase 2C" J.Biol.Chem.268. 133-137 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] K.Fukunaga, L.Stoppini, E.Miyamoto & D.Muller: "Long-term potentiation is assosiated with an increased activity of Ca^<2+>/calmodulin-dependent protein kinase II" J.Biol.Chem.268. 7863-7867 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] M.Ohgushi, K.Kugiyama, K.Fukunaga, T.Murohara, S.Sugiyama, E.Miyamoto and H.Yasue: "Protein kinase C inhibitors prevent impairment of endothelium-dependent relaxation by oxidatively modified LDL" Arteriosclerosis and Thrombosis. 13. 1525-1532 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Goto, S.Nagahiro, K.Korematsu, Y.Ushio, E.Miyamoto and W.Hofer: "Cellular colocalization of calcium/calmodulin-dependent protein kinase II and calcineurin in the rat cerebral cortex and hippocampus" Neurosci.Lett.149. 189-192 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] F.Arakane, K.Fukunaga, S.Araki, S.Abe, M.Satake, K.Miyazaki, H.Okamura and E.Miyamoto: "Glycolipids isolated from Aplysia kurodai can activate cyclic adenosine 3', 5'-monophosphate-dependent protein kinase from rat brain" J.Neurochem.62. 86-93 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Yano, K.Fukunaga, Y.Ushio and E.Miyamoto: "Activation of Ca^<2+>/calmodulin-dependent protein kinase II and phosphorylation of intermediate filament proteins by stimulation of glutamate receptors in cultured rat cortical astrocytes" J.Biol.Chem.269. 5428-5439 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] K.Fukunaga, H.Yamamoto & T.R.Soderling: Excitatory amino acids and protein kinases. In : Fidia Research, Foundation Symposium Series, Vol.9, Excitatory amino acids (Eds.R.P.Simon). Thieme Medical Publishers, Inc., New York, 159-165 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] K.Fukunaga: "Activation of Ca^<2+>/calmodulin-dependent protein kinase II and protein kinase C by glutamate in cultured rat hippocampal neurons" J.Biol.Chem.267. 22527-22533 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] K.Fukunaga: "Dephosphorylation of autophosphorylated Ca^<2+>/calmodulin-dependent protein kinase II by protein phosphatase 2C" J.Biol.Chem.268. 133-137 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] K.Fukunaga: "Long-term potentiation is associated with an increased activity of Ca^<2+>/calmodulin-dependent protein kinase II" J.Biol.Chem.268. 7863-7867 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 福永浩司: "細胞情報伝達機構におけるCa^<2+>/カルモデュリン依存性プロテインキナーゼの役割" 日薬理誌. 101. 355-369 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] F.Arakane: "Glycolipids isolated from Aplysia kurodai can activate cyclic adenosine 3′,5′-monophosphate-dependent protein kinase from rat brain" J.Neurochem.62. 86-93 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] S.Yano: "Activation of Ca^<2+>/calmodulin-dependent protein kinase II and phosphorylation of intermediate filament proteins by stimulation of glutamate receptors in cultured rat cortical astrocytes" J.Biol.Chem.(in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] K.Fukunaga: "In:Fidia Research,Foundation Symposium Series,Vol.9,Excitatory amino acids (Eds.R.P.Simon),Excitatory amino acids and protein kinase" Thieme Medical Publishers,Inc.,New York, 7 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] H.Yamamoto: "Ischemia-induced loss of brain calcium/calmodulin-dependent protein kinase II" J.Neurochem.58. 1110-1117 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Morioka: "Regional and temporal alterations in Ca^<2+>/calmodulin-dependent protein kinase II and calcineurin in the hippocampus of rat brain after transient forebrain ischemia" J.Neurochem.58. 1798-1809 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Yamakawa: "Occurrence of Ca^<2+>/calmodulin-dependent protein kinase 2 in various cultured cells" Biomedical Res.13. 173-179 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Yamakawa: "Activation of Ca^<2+>/calmodulin-dependent protein kinase II by stimulation with bradykinin" Brain Res.597. 220-226 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Fukunaga: "Activation of Ca^<2+>/calmodulin-dependent protein kinase II and protein kinase C by glutamate in cultured rat hippocampal neurons" J.Biol.Chem.267. 22527-22533 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Fukunaga: "Dephosphorylation of autophosphorylated Ca^<2+>/calmodulin-dependent protein kinase II by protein phosphatase 2C" J.Biol.Chem.268. 133-137 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Fukunaga: "Fidia Research Fundation Symposium Series,Vol.9,Excitatory Amino Acids" Thieme Medical Publishers,Inc.,New York, 292 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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